Pain Medical Musing

Exciting discovery! Hydroxymethylglutaryl-CoA (HMG-CoA) Reductase is involved in cholesterol metabolism and cholesterol pills block that enzyme. People with a less functioning version of that enzyme ended up with statin induce myopathy according to one study. Another study found it implicated in some limb-girdle muscular dystrophy and treatable with a compound that helps this enzyme – called oral mevalonolactone.

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I’m a big advocate of B12 for nerve damage pain but have added B6 to my regimen as came across article using it for drug induced neuropathy. Been previously shown to help carpal tunnel symptoms. B6 is touchy as 400 mg can cause nerve damage so best stick to 100 mg/day.

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Dogs cannot make vitamin D – not even from sun and hence are totally dependent on diet. Osteoarthrtis in humans is only  protected in humans with HIGH vitamin D levels. Might this apply to my dog as well?

Below article discusses the potential need for Vitamin D. Deficiencies were common:

Thirty-three dogs (71·7 %) had 25(OH)D values below the previously reported minimum concentration indicating sufficient vitamin D status of 100 ng/ml”

Young, Lauren R., and Robert C. Backus. “Oral vitamin D supplementation at five times the recommended allowance marginally affects serum 25-hydroxyvitamin D concentrations in dogs.” Journal of nutritional science 5 (2016).

https://www.cambridge.org/core/services/aop-cambridge-core/content/view/FFBAD4E956A376301E5DFC12F0E1C252/S2048679016000239a.pdf/oral-vitamin-d-supplementation-at-five-times-the-recommended-allowance-marginally-affects-serum-25-hydroxyvitamin-d-concentrations-in-dogs.pdf

Importance of Vitamin D in dogs so far:

In veterinary medicine, many investigators have reported associations between low serum 25(OH)D concentrations and canine mast cell tumour(16) , chronic kidney disease (17), congestive heart failure(18) , inflammatory bowel disease (19) and cancer (10)

16 Wakshlag JJ, Rassnick KM, Malone EK, et al. (2011)
Cross-sectional study to investigate the association between vitamin D status and cutaneous mast cell tumours in Labrador retrievers. Br J Nutr 106, S60–S63

17 Gerber B, Hassig M & Reusch CE (2003) Serum concentrations of 1,25-dihydroxycholecalciferol and 25-hydroxycholecalciferol in clinically normal dogs and dogs with acute and chronic renal failure. Am J Vet Res 64, 1161–1166

18 Kraus MS, Rassnick KM, Wakshlag JJ, et al. (2014) Relation of vitamin D status to congestive heart failure and cardiovascular events in dogs. J Vet Intern Med 28, 109–115

19 Gow AG, Else R, Evans H, et al. (2011) Hypovitaminosis D in dogs with inflammatory bowel disease and hypoalbuminaemia. J Small Anim Pract 52, 411–418.

10 Selting KA, Sharp CR, Ringold R, et al. (2014) Serum 25-hydroxyvitamin D concentrations in dogs – correlation with health and cancer risk. Vet Comp Oncol (epublication ahead of print version 8 July 2014).

ARTHRITIS BIG ISSUE and NEED FOR HIGH VITAMIN D LEVELS

What is little known in human studies is only high levels fully protect people

only HIGH levels fully protect mono sufferers from getting MS:
Munger, Kassandra L., et al. “Serum 25-hydroxyvitamin D levels and risk of multiple sclerosis.” Jama 296.23 (2006): 2832-2838.
https://jamanetwork.com/journals/jama/fullarticle/204651/

“HIGH circulating levels of vitamin D are associated with a lower risk of multiple sclerosis.”

HIGH levels fully help protect subjects from heart disease:

J Prev Med Public Health. 2017 Jul; 50(4): 278–281.
The Big Vitamin D Mistake
Dimitrios T. Papadimitriou
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5541280/pdf/jpmph-50-4-278.pdf

HIGH  levels are helpful in lupus:

Pakchotanon, Rattapol, et al. “Randomized Double-Blind Controlled Trial To Evaluate Efficacy Of Vitamin D Supplementation Among Patients With Systemic Lupus Erythematosus.” Journal of Southeast Asian Medical Research 4.1 (2020): 24-32. https://www.jseamed.org/index.php/jseamed/article/view/57

AND Most importantly, only HIGH levels gave best protection against Osteoarthritis.

In a Framingham study of osteoarthritis only subjects in the Upper 1/3 blood levels of vitamin D were protected from osteoarthritis progression: Relation of Dietary Intake and Serum Levels of Vitamin D to Progression of Osteoarthritis of the Knee among Participants in the Framingham Study Timothy E. McAlindon et al Ann Intern Med. 1996;125(5):353-359.

http://annals.org/article.aspx?articleid=709914

“Risk for progression increased threefold in participants in the middle and lower tertiles for both vitamin D intake (odds ratio for the lower compared with the upper tertile, 4.0 [95% CI, 1.4 to 11.6]) and serum levels of vitamin D (odds ratio for the lower compared with the upper tertile, 2.9 [CI, 1.0 to 8.2]).”

This is huge with “normal” and low levels getting THREE times the osteoarthritis rates. However, where I live vitamin D deficiency is rampant and there seems to be no understanding that knee replacement might be in part related to low vitamin D levels.

 Suspect same seems to go with canines.

Dogs carry huge risk of osteoarthritis yet there is little research into need for vitamin d.

Initial article used:

2·3 μg vitamin D 3 /kg BW exp 0·75

Exponenting the weight comes from studies:
Sidhu KS. Basis for body weight exponent (0.75) as a scaling factor in energy metabolism and risk assessment. J Appl Toxicol. 1992 Oct;12(5):309-10
https://pubmed.ncbi.nlm.nih.gov/1447474/

1 mcg vitamin D is equal to 40 IU

10 kg exp 0.75 comes to 5.6 kg

Results work out to 560 u/day for a 10 kg dog (400 u = one drop pediatric – so one drop for 3 days and 2 drops on forth day)

Gave my 10 k cocker spaniel his first drop today….  More heavy set dogs are going to need it more…

addendum – vit d supplementation might help itch in dogs:

Klinger, Christoph J., et al.
Vitamin D shows in vivo efficacy in a placebo‐controlled, double‐blinded, randomised clinical trial on canine atopic dermatitis.
Veterinary Record 182.14 (2018): 406-406.
https://www.rxvitamins.com/rxvitaminsforpet/wp-content/uploads/2018/03/Vitamin-D-Study.pdf

“After eight weeks of treatment, patients who received cholecalciferol showed significantly less pruritus than patients from the placebo group (P<0.0001)” – actually cut it in half! I’m hoping my dog will scratch less…

Since it was found that high dose B12 shots can almost double life expectancy of victims with ALS, the use of B12 shots has taken a new life

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There can be a significant depression issue in chronic pain in which, if you scratch the surface, you find significant underlying anger is actually the issue. Inability to deal with the anger leads to significant depression and self-flagellation and increase suffering. I attempt to suggest to patient to say out loud “I forgive you” in regards to others but finds subjects choke up on that. Now it look like a way in, is to do loving kindness meditation (Tong Len taking and giving). This involves meditation plus imagining breathing in the black “pain” of others while breathing out an aura of happiness to others. My feeling is that doing that to ones you hate could help the issue and give you a sense of relief.

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Spinal cord stimulation is often used as a last resort. To start with, that is a mistake.

Dr. K Kumar pioneered efforts to use spinal stimulation:

Here is a list of some of his articles:
https://scholar.google.ca/scholar?q=Kris+Kumar+spinal+cord+stimulation&hl=en&as_sdt=0&as_vis=1&oi=scholart

I have been practicing long enough in his town to hear him speak and one thing always stuck with me. He bemoaned how long it took for subjects to get to him for treatment as he felt early intervention improved results. Some years ago at a conference, spinal stimulation was discussed but the neurosurgeon was unaware of Dr. Kumar’s 22+ years of experience culminating in that revelation. I was shocked.

So, subjects are seen late, and fail to achieve adequate relief with spinal stimulation even with new modes being used- then what do you do? I try IV pamidronate, ketamine and even methadone might have a place. Now, it looks like adding a stimulator more externally to the outlet of the spinal cord where the dorsal root ganglion is, could make the difference.

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Chronic diseases with negative “blood work” might in fact be  a cytokine inflammation disease. Moderate fibromyalgia has now be found to be a cytokine inspired disease.

I wrote about importance of cytokines 12 years ago:
Cytokine Inflammation Diseases Will Be the Diseases of the 21st Century
http://painmuse.org/?p=361

Then connection to multiple diseases were seen (headaches, irritable bowel, diabetes, alzheimer’s, chronic pancreatitis, chronic fatigue, depression and now depression.

Back in 2013 I wrote a draft that was never published:
“Could Elevated Cytokines Become a Test For Fibromyalgia (FM)?” Now it has.

Below is an update on tests in Fibromyalgia and cytokine relation

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I have found for years that pure cannabinoid (CBD) seemed to have little impact in significant = more likely neuropathic pain.  I tired to get subjects to at least have 1/4 portion of THC but elderly subjects would have nothing to do with spacing out meds. Now the animal model has shown that pure CBD has little impact on neuropathic pain. Marijuana sites pride themselves in regulating cannabis doses as they consider doctors  idiots when it comes to that. However, when you look at their titrations, it is very down-scaled and not likely to have impact for 3-6 weeks. Due to expense, many of my trial users give up on the med.

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Now that it looks like Rheumatoid Arthritis could be infection driven, the benefits in a study of Clavulin (amoxicilin + clavulanic acid) needs revisiting. It has been know for a long time that certain antibiotics have “anti-inflammatory properties”. Now it might be interpreted that they control bacteria that could augment inflammation. A study of plain amoxicillin did not work.

Does that mean that Clavulin controls this inflammation by having wider antibiotic spectrum and should it engender new respect? Could certain antibiotics work like they do in rheumatoid arthritis and reduce inflammation?

Anti-inflammatories “NSAID’s” work poorly in ankylosing spondylitis. Methotrexate does not seem to help.

Prednisone helps but high dose is needed to get any initial response and cannot be used long-term by self especially related to osteoporosis.

Pamidronate is a game changer in chronic back pains particularly where inflammation is missed.  Mixing with prednisone/steroid is possible.

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Recent Study found a strain of previously unrecognized strain of Subdoligranulum in gut was associated with Rheumatoid arthritis (RA) autoantibodies. This bacterium, if introduced into guts of mice, replicated the arthritis seen in humans. This strain is only seen in RA victims.

So, both gut bacterial and periodontal disease can potentially trigger antimmune responses. This leads to new implications on prevention and treatment of Rheumatoid arthritis.

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Our medical college has taken upon themselves the task of antagonizing doctors to point many clinic will no longer even prescribe opioids. They called their program “educational” but demanded doctors respond to them is 2 weeks or else face discipline. No where else in Canada is it that short – BC has 2 “working” weeks which ends up 3 weeks. Some 20 years ago I went to see The then Registrar, Dr. Kendel, and told him 2 weeks was too short but he seemed more concerned that doctors did not take the letter seriously. I got in trouble over that and retired over it.

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Most drugs have little effect on back pain or back pain with sciatica. Surprisingly, a combination of Buprenophine and Pregabalin did seem to make a difference in milder back pain cases.

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I have tested testosterone levels in my chronic pain female patients and found none of them had any detectable levels; they should have some. I have recently upgraded this to show its growing importance – cutting Fibromyalgia pain in half is exciting.

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Spinal stensois is a horrible disease often thought that surgery is the only outlet (though steroid blocks might have some “limited” effect).  Now again pamidronate has been shown to stem tide of pain with a mean improvement of 40%. Not a controlled trial; but still encouraging. Old study but new to me…

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Studies of too little, too short or too narrow a scope are associated with poor outcome and I am accumulating a list of poorly done studies as I am just fed up. I hope authors take note. I will take me awhile to go thru a compilation of studies I have.

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Selecting people with mildly abnormal hemoglobin A1C (prediabetic), authors found the introduction of Metformin 500 mg twice daily could dramatically relieve widespread pains. Article had to be pulled because consents were iffy and they didn’t have enough in “control group” to prove it didn’t work in non-diabetics. This was May 2019; I have been waiting for them to get consents and a big enough control group but treatment study was never republished. This has remained a secret.

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